title: Fatty liver is associated with transcriptional downregulation of stearoyl-CoA desaturase and impaired protein dimerization.
abstract: OBJECTIVE
  We evaluated the modulation of liver stearoyl-CoA desaturase-1 (Scd1) by dietary factors and insulin resistance (IR) in two experimental models of high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). The first model included Sprague Dawley (SD) rats that developed NAFLD without IR, and the second one included a rat model of genetic IR and cardiovascular disease, the spontaneously hypertensive rats (SHR) and its normotensive, insulin-sensitive control Wistar-Kyoto (WKY). The adult rats were given standard chow diet (CD) or HFD for 10 weeks. In all the animals, we explored the hepatic Scd1 transcriptional activity and protein levels.
  
  
  RESULTS
  HFD-fed rats of both strains developed severe NAFLD. Liver abundance of Scd1 mRNA was significantly decreased in HFD-fed rats regardless of the strain; SD-CD: 235±195 vs. SD-HFD 4.5±2.9, p<0.0004, and SHR-CD: 75.6±10.8 vs. SHR-HFD: 4.48±17.4, and WKY-CD: 168.7±17.4 vs. WKY-HFD: 12.9±17.4, p<0.000001 (mean±SE, ANCOVA adjusted by HOMA). Analysis of liver Scd1 protein expression showed a particular pattern in the HFD groups, characterized by the presence of high levels of a monomeric protein band (32.2-36.6 Kda, p<0.003) and decreased levels of a dimeric protein band (61.9-66.1 Kda, p<0.02) regardless of the rat strain. Pharmacologic intervention with the peroxisome proliferator-activated receptor α agonist clofibrate reverted the liver phenotype and significantly modified the hepatic Scd1 transcriptional activity and protein expression.
  
  
  CONCLUSIONS
  Diet-induced fatty liver is associated with the downregulation of hepatic Scd1 transcript and de-dimerization of the protein, and these changes were not much affected by the status of peripheral IR.
authors.affiliation: Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Tomas
authors.initials: T
authors.lastname: Fernández Gianotti
authors.forename: Adriana
authors.initials: A
authors.lastname: Burgueño
authors.forename: Noelia
authors.initials: N
authors.lastname: Gonzales Mansilla
authors.forename: Carlos Jose
authors.initials: CJ
authors.lastname: Pirola
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*
chemical_list: D013230:Stearoyl-CoA Desaturase